Aging
Project: Bioinformatic analysis of transcriptome data in age research. (M. Fichtner)
The focus of the project lies on age-related protein damage... (read more)
The focus of the project lies on age-related protein damage that leads to aggregates. These cannot be degraded anymore and therefore accumulate until the cell suffers from major functional inhibitions and finally triggers apoptosis. The goal is to determine what are the most or also least favoured targets in terms of aggregation. Also information from structure and prominent aggregates will be included. Furthermore connections and functions will be examined by computational modeling and the use of transcriptome data.
Project: Molecular processes affected during immunosenescence. (H. Stark, M. Fichtner)
Our society gets older... (read more)
Our society gets older, people live longer. The price we pay: infectious diseases can easier overcome the immune system. Like all organs, the immune system does not function flawlessly in old age. University and non-university research institutes and two companies joined forces in the “GERONTOSHIELD” project to investigate why our immune defence is getting weaker when we become old. The strategic objective of the project is to draw on a Systems Biology-driven approach to understand the molecular processes affected during immunosenescence to derive strategies to overcome them in order to establish immune interventions tailored for the elderly.
Project: Bioinformatic analysis of the adaptive cellular stress response. (P. Moeller)
We want to investigate the adaptive response... (read more)
We want to investigate the adaptive response of signalling networks to stress by using computational modeling. Organisms confronted with harmful assaults can react in surprising ways. Depending on the property of the stress stimuli, the reaction of the organisms has quite a variety. They can become resistant, more vital, or they die. Until now less is known about the molecular mechanisms that underlie these responses. Our expectation is to give a better understanding of stress responses and find some potential targets for modern medicine.
Liver metabolism
Project: Modeling the pathogenesis of pericentral steatosis – Influence of oxygen on fat accumulation and production of reactive oxygen species. (J. Schleicher)
We will verify the general mechanisms in the pathogenesis of zonated fat accumulation... (read more)
We will verify the general mechanisms in the pathogenesis of zonated fat accumulation and uncover the role of the altered oxygen supply in steatotic livers for the production of reactive oxygen species (ROS). The project is aimed to propose specific hypotheses in regard to a reduced ROS burden during ischemia of steatotic livers. This ought to happen through an iterative cycle of modeling and experiments. In a first step, we implement models (ordinary differential equations) of hepatic lipid metabolism and ROS production for the fat-induced and the alcohol-induced fatty liver pathogenesis.
Project: Modeling the zonation of liver lipid metabolism. (C. Tokarski)
Metabolism of human liver cells differs with respect to the degree of expression of several enzymes... (read more)
Metabolism of human liver cells differs with respect to the degree of expression of several enzymes. This leads to differences in activity of major metabolic pathways in the periportal and perivenous zones of the liver. In a preliminary model the most important reaction pathways of liver lipid metabolism are subsumed to a minimal model including fatty acid uptake, degradation via betaoxidation and triacylglyceride synthesis and ketone body formation as well as denovo synthesis of fatty acids. To model the zonation of liver lipid metabolism several onecell models are connected in series as compartments having inflow and outflow of metabolites..
Project: Mathematical modelling of host-pathogen interactions. (S. Duehring)
The polymorphic yeast Candida albicans and the filamentous fungus Aspergillus fumigatus are the most important life-threatening human pathogenic fungi... (read more)
The polymorphic yeast Candida albicans and the filamentous fungus Aspergillus fumigatus are the most important life-threatening human pathogenic fungi. Both fungi have developed multiple strategies to attack and evade the human immune system. Using differential equation systems, dynamic optimization, evolutionary game theory and other biomathematics and bioinformatics methods we analyze the struggle between these fungi and the human immune system. For this we analyse the dynamics of the populations to find stable equilibria and study payoff matrices in view of aggressive strategies versus peaceful coexistence. In examining the switch between different equilibria we determine the conditions under which dimorphic fungi make phenotypic transitions and become pathogenic.
Project: Dynamic optimization as a tool to study unicellular organisms. (J. Ewald)
Organisms and their traits are shaped by evolution leading to an optimized metabolism and cell behaviour... (read more)
Organisms and their traits are shaped by evolution leading to an optimized metabolism and cell behaviour. In this project, we use dynamic optimization, a widely used tool in engineering, to understand the optimality principles in biological systems with respect to time, which is often neglected by other approaches. Specifically, we want to understand the principles behind the regulation of cell metabolism and the interaction of pathogenic microorganisms with the immune system. Due to the embedding of the project in the Transregio "FungiNet (B2)", a close cooperation with experimentalists ensures the validation of the gathered hypotheses.